AHFS Class:

• Corticosteroids 52:08.08

Generic Name(s):

• Difluprednate

Chemical Name:

• 6α,9-difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate

Molecular Formula:

• C₂₇H₃₄F₂O₇

Difluprednate is a difluorinated corticosteroid.1,2

Postoperative Ocular Inflammation and Pain

Difluprednate ophthalmic emulsion is used for the treatment of inflammation and pain associated with ocular surgery.1,2

Efficacy of difluprednate has been evaluated in 2 randomized, double-blind, placebo-controlled studies in patients who had undergone cataract surgery.1 In these studies, patients with an anterior chamber cell grade of 2 or higher (a cell count of 11 or higher) after cataract surgery were randomized to receive either difluprednate 0.05% ophthalmic emulsion (1 drop 2 or 4 times daily) or vehicle for 14 days, beginning the day after surgery.1 At 8 days postoperatively, reduction of ocular inflammation (anterior chamber cell clearing) or absence of ocular pain was achieved in 22 or 58%, respectively, of patients receiving difluprednate (1 drop 4 times daily) compared with 7 or 27%, respectively, of those receiving vehicle.1 At 15 days postoperatively, anterior chamber cell clearing or absence of ocular pain was achieved in 41 or 63%, respectively, of patients receiving difluprednate (1 drop 4 times daily) compared with 11 or 35%, respectively, of those receiving vehicle.1

Administration

Difluprednate is applied topically in the conjunctival sac of the affected eye(s) as an ophthalmic emulsion.1 Care should be taken to avoid contamination of the emulsion container.1

Patients should refrain from wearing contact lenses during therapy with difluprednate ophthalmic emulsion unless specifically directed by a clinician.3

Difluprednate ophthalmic emulsion may be used in conjunction with other topical ophthalmic drugs such as β-adrenergic blocking agents, carbonic anhydrase inhibitors, α-agonists, cycloplegics, and mydriatics.3 If the patient is receiving more than one topical ophthalmic drug, the drugs should be administered 10 minutes apart from difluprednate administration.3

Dosage

The recommended initial adult dosage of difluprednate for the treatment of postoperative inflammation and pain in patients who have undergone ocular surgery is 1 drop of a 0.05% emulsion in the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.1 After 2 weeks of therapy, dosage should be reduced to 1 drop twice daily for 1 week and then gradually tapered according to response.1

Special Populations

No special population recommendations at this time.3

Contraindications

Most active viral diseases of the cornea and conjunctiva (including epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, and varicella [chickenpox]); mycobacterial infection of the eye; and fungal diseases of ocular structures.1

Known hypersensitivity to difluprednate, other corticosteroids, or any ingredient in the formulation.3

Warnings/Precautions

Ocular Effects

Glaucoma (with optic nerve damage and defects in visual acuity and fields of vision) may occur with long-term use of corticosteroids.1 Corticosteroids should be used with caution in patients with glaucoma.1 Intraocular pressure should be monitored if difluprednate is used for 10 days or longer.1

Posterior subcapsular cataract formation also may occur with use of corticosteroids.1

Wound Healing Complications

Use of corticosteroids after cataract surgery may delay healing and increase the incidence of bleb formation.1 In conditions causing thinning of the cornea or sclera, perforations have been reported following use of topical corticosteroids.1

Careful monitoring, including slit-lamp biomicroscopy and fluorescein staining when appropriate, is necessary in patients requiring difluprednate therapy for longer than 28 days.1,3

Increased Susceptibility to Infections

Prolonged use of corticosteroids may increase the risk of secondary ocular infections.1 In acute purulent conditions, corticosteroids may mask infection or exacerbate existing infection.1 If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.1

Use of ophthalmic corticosteroids may prolong and exacerbate ocular viral infections (e.g., herpes simplex).1 Difluprednate should be used with extreme caution in patients with a history of herpes simplex virus infection.1

Fungal infections of the cornea are particularly prone to develop following long-term use of ophthalmic corticosteroids.1 The possibility of fungal infection must be considered in patients receiving corticosteroids who present with persistent corneal ulceration.1 Fungal culture should be obtained when appropriate.1

Specific Populations

Pregnancy

Category C. (See Users Guide)1

Lactation

Systemically administered corticosteroids distribute into milk and may suppress growth, interfere with endogenous corticosteroid production, or cause other adverse effects.1 It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in milk; caution if used in nursing women.1,3

Pediatric Use

Safety and efficacy not established in pediatric patients.1,3

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Common Adverse Effects

Adverse ocular effects reported in 5-15% of patients receiving difluprednate include corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis.1 Adverse ocular effects reported in 1-5% of patients include reduced visual acuity, punctate keratitis, eye inflammation, and iritis.1

No formal drug interaction studies have been performed to date.3

Description

Difluprednate is a difluorinated corticosteroid.1,2 The drug is a derivative of prednisolone2 and is structurally similar to other corticosteroids.1 Corticosteroids inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.1 Although the precise mechanism of the ocular effects of corticosteroids is unknown, corticosteroids are thought to act by inducing phospholipase A₂ inhibitory proteins (collectively referred to as lipocortins); these proteins are postulated to control the biosynthesis of potent inflammatory mediators (e.g., prostaglandins, leukotrienes) by inhibiting the release of their common precursor, arachidonic acid.1

Following ophthalmic administration for 7 days, blood concentrations of difluprednate were below the limit of detection (50 ng/mL), suggesting that systemic absorption of the drug is limited.1

Advice to Patients

Importance of learning and adhering to proper administration techniques to avoid contamination of the tip of the emulsion container.1

Importance of not wearing contact lenses during therapy with difluprednate unless specifically directed by a clinician.1,3

Importance of administering different topical ophthalmic preparations 10 minutes apart from difluprednate administration.3

Risks of adverse ocular effects, wound healing complications, and ocular infections.1,3 Consult a clinician if pain develops or if redness, itching, or inflammation worsens.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Sirion Therapeutics, Inc. Durezol^® (difluprednate) ophthalmic emulsion 0.05% prescribing information. Tampa, FL; 2008 Sep.

2. Stevens E. Sirion Therapeutics announces FDA approval of Durezol^® for treatment of postoperative ocular inflammation and pain. Reuters . 2008 Jun 24. From Reuters website ([Web]).

3. Sirion Therapeutics, Tampa, FL: Personal communication.